Recent technological advances in nuclear magnetic resonance spectroscopy (NMR) permits the assessment of tissue metabolic health through spectroscopic measurements of intact functioning tissues in vitro. the proposed study applies this proven technology to the assessment of etiologic factors which predispose the cornea to loss of transparency. NMR spectroscopy is a nonperturbing analytical method which permits analysis of the underlying metabolic events which preceed loss of transparency and concomitant decline in vision. Inital resu ts in our laboratories have demonstrated the following: (1) NMR spectroscopy of intact cornea in vitro yields profiles of the high-energy phosphates of metabolism with data quality similar to that obtained from muscle, lens, and other organs studied; (2) from these spectra, time-course data can be obtained for the state of ATP, ADP, inorganic oathophosphate and the phosphorylated sugars of glycolysis; (3) using time-course studies the degree of stress that the tissue can withstand before exhibiting irreversible changes, assessed both metabolically and histologically and histologically, can be measured; (4) intracornea pH can be accurately determined from the resonance shift position of inorganic orthophosphate; and (5) upon completion of such time-course experiments the cornea tissue analyzed can be evaluated by histological techniques since the tissue is not in any way destroyed as a result of the metabolic measurement. Our initial work suggests that the following experimetns be carried out: (1) the identity and quantity of all phosphatic corneal metabolites which contribute to the phosphorus NMR spectrum be determined, included in this aspect is the chemical characterization of phosphorus-containing substances whose signals have not previously been identified in intact tissues; (2) the effects of temperature, pH, osmolariaty (hyper- and hypoosmolar effects), and certain bulk ions on the time-course of cornea metabolic activity must be assessed; (3) histological changes must be correlated with the metabolic changes to determine metabolic-structural factors leading to loss of transparency; (4) the effects of endothelial and epithelial loss on phosphorus metabolic profiles correlated with histological changes must be assesse; (5) Finally, in so far as is possilble, findings from the animal model studies proposed herein (rabbit and bovine corneas) must be related to parallel studies on human tissue. Ultimately, these studies will provide a unique metabolic and histologic perspective about the external factors (eg., buffer pH, osmolarity, temperature) which enhance corneal preservation by reducing the rate of tissue metabolism and morphologic deterioration.